Journal of Bioenergetics and Biomembranes最新文献

{"title":"Mitofusin 2 orchestrates mitochondrial metabolic homeostasis and suppresses cutaneous squamous cell carcinoma by stabilizing ER-mitochondria contacts.","authors":"Xianpeng Ma, Jing Liu, Xiao Shao, Yupeng Huang, Guangyao Hu","doi":"10.1007/s10863-026-10132-y","DOIUrl":"https://doi.org/10.1007/s10863-026-10132-y","url":null,"abstract":"<p><p>This study aimed to elucidate the biological role of Mitofusin 2 (Mfn2) in cutaneous squamous cell carcinoma (cSCC) and evaluate how its regulation of mitochondria-associated membranes (MAMs) may suppress tumor progression by reshaping mitochondrial metabolic homeostasis and apoptosis. We compared Mfn2 expression between normal keratinocytes (HaCaT) and cSCC cells (A431), establishing a stable Mfn2-overexpressing (Mfn2-OE) A431 model. Structural impacts on ER-mitochondrial contacts and MAMs were evaluated using immunofluorescence, STED super-resolution microscopy, TEM, and subcellular fractionation (VDAC1/IP3R/Grp75). Functional assays assessed ER-mitochondrial calcium transport (probes), lipid peroxidation/ROS (C11-BODIPY/DCFH-DA), mitochondrial membrane potential, and ATP levels (JC-1/ATP assays). Mitochondria-dependent apoptosis (Bcl-2/p53/Cytochrome c/Caspase-3) was analyzed via flow cytometry, TUNEL, and Western blot. Phenotypes were assessed using CCK-8, EdU, colony formation, and Transwell assays. In vivo xenografts in nude mice were monitored, with H&E/IHC analysis. Proteomics and untargeted metabolomics (LC-MS) were performed (n = 6/group). Mfn2 protein levels were lower in A431 cSCC cells than in HaCaT keratinocytes. Mfn2-OE enhanced ER-mitochondrial contacts, increased MAMs, and stabilized the VDAC1-Grp75-IP3R complex. This enhanced calcium transport, reduced ROS/lipid peroxidation, stabilized MMP, and decreased ATP. Mfn2-OE inhibited Bcl-2, promoted p53 mitochondrial translocation and Cytochrome c release, activating Caspase cascades. Both in vitro and in vivo, Mfn2-OE suppressed proliferation, invasion, and tumor growth. Proteomics/metabolomics revealed metabolic reprogramming involving energy metabolism, lipid metabolism, and redox balance. Mfn2 may act as a tumor-suppressive regulator in the A431 cSCC model by stabilizing MAMs, remodeling mitochondrial metabolic homeostasis, and activating mitochondria-dependent apoptosis.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of aquatic exercise on nociceptive behavior, systemic inflammation, and skeletal muscle redox status in healthy and reserpine-treated rats.","authors":"Arife Apaydın Pınar, Muaz Belviranli, Nilsel Okudan","doi":"10.1007/s10863-026-10139-5","DOIUrl":"https://doi.org/10.1007/s10863-026-10139-5","url":null,"abstract":"<p><p>This study investigated whether a 21-day swimming exercise protocol administered concurrently with reserpine exposure modifies nociceptive behavior, serum serotonin and TNF-α levels, and skeletal muscle redox markers in a reserpine-induced fibromyalgia (FM) model. Twenty-four female rats were randomly allocated into Control (CON), Reserpine (RES), Exercise (EX), and RES + EX groups. FM was induced via subcutaneous reserpine administration (1 mg kg^-1 day^-1 for 3 days). Swimming groups exercised for 60 min day^-1 over 21 days. Behavioral hyperalgesia was evaluated using the cold-plate test. Serum tumor necrosis factor-alpha (TNF-α) and serotonin, alongside skeletal muscle malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC) were quantified using ELISA. Compared with CON, the RES group showed shorter cold-plate latency, lower serum serotonin, higher serum TNF-α, higher muscle PC, and lower muscle SOD and GSH (p ≤ 0.05). MDA was higher in RES than in EX and RES + EX, but a significant difference between RES and CON was not reported. Swimming increased cold-plate latency in RES + EX compared with RES on days 7, 14, and 21 (all p < 0.001). RES + EX also showed higher serotonin and lower TNF-α than RES (p ≤ 0.05). Muscle PC was lower and SOD/GSH were higher in RES + EX than in RES for the reported comparisons; however, GSH remained lower in RES + EX than in EX. TAC did not differ significantly among groups (p = 0.228). Swimming exercise attenuated reserpine-associated cold allodynia and was associated with more favorable serum serotonin/TNF-α profiles and skeletal muscle redox markers.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APPL1 attenuates DHEA-induced oxidative injury in granulosa cells by enhancing mitophagy and suppressing ferroptosis: implications for polycystic ovary syndrome.","authors":"Shentao Lu, Xueru Yang, Yingxia He, Hua Linghu, Xuemei Fu","doi":"10.1007/s10863-026-10141-x","DOIUrl":"10.1007/s10863-026-10141-x","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a complex endocrine disorder frequently associated with granulosa cell dysfunction. However, its underlying molecular mechanisms remain unclear. Therefore, we aimed to examine the role of APPL1 in PCOS and determine whether it attenuates oxidative stress and ferroptosis by modulating mitophagy in granulosa cells. An in vitro PCOS model was established by treating KGN cells with dehydroepiandrosterone (DHEA), with or without concurrent APPL1 overexpression. An in vivo PCOS rat model was established by DHEA injection, followed by intraovarian lentiviral delivery to overexpress APPL1. Oxidative stress, ferroptosis, and mitophagy markers were also evaluated. Mdivi-1, the DRP1/mitochondrial fission inhibitor, was used to examine this pathway. APPL1 expression was significantly reduced in DHEA-treated KGN cells and PCOS rat ovaries. APPL1 overexpression markedly attenuated DHEA-induced oxidative stress and ferroptosis in vitro, as evidenced by reduced ROS, MDA, 8‑OHdG, Fe²⁺, and ACSL4 levels, together with restored antioxidant enzyme activities and GPX4/SLC7A11 expression. Concurrently, APPL1 overexpression enhanced mitophagy, as shown by an increased LC3-II/LC3-I ratio and decreased p62 and TOMM20/COX IV levels. Treatment with Mdivi-1 attenuated these protective effects. APPL1 overexpression improved estrous cyclicity, attenuated hyperandrogenism, ameliorated ovarian morphology, and alleviated ovarian oxidative stress and ferroptosis in PCOS rats. APPL1 protected granulosa cells against DHEA-induced oxidative injury and ferroptosis by enhancing mitophagy in preclinical PCOS models. These findings provide mechanistic insights into PCOS pathogenesis and identify the APPL1-mitophagy axis as a potential target for PCOS intervention.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics analysis, machine learning, and experimental validation reveal that ACSL1 drives myocardial ischemia reperfusion injury via ferroptosis.","authors":"Shuiling Yuan, Zhong Xie, Chunchen Xia, Shiqi Yang, Jiming Zhou","doi":"10.1007/s10863-026-10138-6","DOIUrl":"10.1007/s10863-026-10138-6","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following an acute myocardial infarction (AMI). Ferroptosis, a type of regulated cell death driven by iron and marked by lipid peroxidation, has attracted increasing attention for its pivotal role in the pathogenesis of MIRI. It has been reported that acyl-CoA synthetase long chain family member 1 (ACSL1), a ferroptosis promoter, could mediate ferroptosis of myocardial cells during AMI. However, the specific function and mechanism of ACSL1 in AMI are still unclear. Differentially expressed genes in AMI were identified from the Gene Expression Omnibus (GEO) databases (GSE166780 and GSE97320), and ferroptosis-related genes were acquired from the PathCards database. Through integrated analysis of the two genomes, ferroptosis-related genes in AMI were identified. Then, the identified genes were subjected to cross-validation using three machine learning algorithms (LASSO, SVM-RFE, and RF), ultimately identifying characteristic genes. ACSL1, Forkhead box protein O4 (FOXO4), tripartite motif-containing protein 25 (TRIM25), and GPX4 protein levels were detected using western blot. Cell viability and apoptosis were Cell Counting Kit-8 (CCK-8) and flow cytometry. Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Fe2+ level, lipid reactive oxygen species (ROS) level, and GSH level were examined using commercial kits. Flow cytometric analysis of mitochondrial membrane potential using JC-1. Binding between FOXO4 and ACSL1 promoter was predicted by JASPAR and verified using dual-luciferase reporter and ChIP assays. The stability of ACSL1 was assessed by CHX assay. Interaction between TRIM25 and ACSL1 was verified using Co-immunoprecipitation (CoIP) assay. The effect of ACSL1 on myocardial injury was detected using a mouse MIR model. After screening and identification, ferroptosis-related gene ACSL1 in AMI was selected for this study. ACSL1 expression was increased in AMI patients and Ischemia/Reperfusion (H/R)-treated AC16 cells. H/R-triggered AC16 cell viability inhibition, and apoptosis, inflammatory response, ferroptosis, and mitochondrial dysfunction promotion were partly abolished by ACSL1 silencing. Mechanistically, FOXO4 activated ACSL1 transcription by binding to its promoter region. TRIM25 facilitated ACSL1 ubiquitination and decreased its protein stability. ACSL1 downregulation could relieve myocardial damage in vivo. ACSL1 was identified as a key ferroptosis-related gene in AMI. Furthermore, FOXO4-activated transcription and TRIM25-mediated ubiquitination-dependent degradation of ACSL1 could affect H/R-induced cardiomyocyte damage and ferroptosis, providing a promising therapeutic target for MIRI treatment.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M2-Exo-derived miR-1227-5p protects against periodontitis through inhibiting USP2-dependent deubiquitination of Drp1.","authors":"Danwei Zhao, Ruifeng Li, Nan Li","doi":"10.1007/s10863-026-10137-7","DOIUrl":"10.1007/s10863-026-10137-7","url":null,"abstract":"<p><p>Periodontitis is a common chronic inflammatory disease with an exaggerated host immune response. M2 type macrophages exert protective properties in periodontitis. This study aimed to investigate the role of M2-Exo-derived miR-1227-5p in periodontitis. M2-Exo were verified using TEM and NTR assay. miRNA and mRNA levels were determined using RT-qPCR. periodontal ligament stem cells (PDLCs) were exposed to LPS in establish in vitro periodontitis model. Gene expression was determined using Western blot and immunofluorescence. The binding sites of miR-1227-5p on USP2 were predicted by TargetScan and verified by luciferase, RNA pull-down, and RIP assays. Deubiquitination of Drp1 was determined using in vitro ubiquitination assay. Cellular behaviors of PDLCs were analyzed by CCK-8, alizarin red staining, and ALP staining. LPS exposure induced mitochondrial dysfunction and suppressed the osteogenesis of PDLCs. M2-Exo-derived miR-1227-5p improved mitochondrial function and promoted the proliferation and osteogenesis of PDLCs. miR-1227-5p directly targeted USP2. USP2 overexpression reversed the effects of miR-1227-5p and improved mitochondrial function and the osteogenesis of PDLCs. Moreover, miR-1227-5p targeted USP2 to inhibit the deubiquitination of Drp1, improving mitochondrial function. Furthermore, M2-Exo-derived miR-1227-5p alleviates periodontitis via regulating USP2/Drp1. Therefore, M2-Exo hold great potential for future clinical applications.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTO-mediated GPX4 m6A modification in ferroptosis-induced DNA damage and inflammatory response during acute lung injury.","authors":"Xiuli Liu, Ying Gu, Fang Yuan","doi":"10.1007/s10863-026-10133-x","DOIUrl":"10.1007/s10863-026-10133-x","url":null,"abstract":"<p><p>To investigate the role of Fat Mass and Obesity-associated Protein (FTO) in acute lung injury (ALI) and elucidate how it regulates ferroptosis via N6-methyladenosine (m6A) modification of glutathione peroxidase 4 (GPX4). ALI models were established in LPS‑stimulated BEAS‑2B cells and mice. FTO expression was modulated by siRNA, inhibitors, or adeno‑associated virus. Ferroptosis, apoptosis, inflammation and DNA damage were assessed by RIP‑qPCR, meRIP‑qPCR, Western blotting and TEM. GPX4 m6A site mutants were constructed. GPX4 mRNA/protein stability and translation were analyzed using actinomycin D and cycloheximide. Establish an LPS-induced ALI mouse model, perform adeno-associated viral knockdown of FTO in lung tissue, and validate in vivo using GPX4 inhibitors. FTO inhibition significantly attenuated LPS-induced ferroptosis, apoptosis, inflammatory responses, and mitochondrial damage. Mechanistically, FTO accelerates GPX4 protein degradation by reducing m6A modification of GPX4, thereby downregulating GPX4 protein expression in a post-transcriptional and post-translational manner. This leads to intracellular iron accumulation, ROS bursts, lipid peroxidation, and DNA damage. Mutating the m6A site in GPX4 or supplementing GPX4 protein effectively reverses the aforementioned damage. Silencing FTO in vivo significantly ameliorates pulmonary tissue pathology, impaired lung function, ferroptosis, and inflammatory responses in mice via a GPX4-dependent pathway, whereas GPX4 inhibition reverses this protective effect. FTO exacerbates ALI by mediating m6A modification of GPX4 and downregulates its protein expression, thereby driving ferroptosis and DNA damage. Targeting the FTO-GPX4 axis may offer novel therapeutic strategies for ALI.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.","authors":"Gino A Kurian","doi":"10.1007/s10863-026-10136-8","DOIUrl":"10.1007/s10863-026-10136-8","url":null,"abstract":"<p><p>Cardiovascular disease is strongly influenced by mitochondrial dysfunction, yet how mitochondrial stress is communicated beyond the affected cell to coordinate systemic responses remains incompletely understood. Mitokines are stress-responsive signaling factors that link mitochondrial perturbation to cellular and interorgan adaptation. These include nuclear-encoded proteins such as fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), as well as mitochondrial-derived peptides including Humanin and MOTS-c. This review critically examines mitokine regulation and signaling in the context of cardiovascular stress, with emphasis on mitochondrial unfolded protein response and integrated stress response pathways, receptor and downstream signaling mechanisms, and the functional divergence among major mitokines. Transient mitokine responses during physiological or metabolic challenge may support metabolic flexibility, cytoprotection, and stress adaptation, whereas persistent elevations of FGF21 and GDF15 in cardiovascular and cardiometabolic disease frequently accompany unresolved mitochondrial stress and adverse clinical phenotypes. Importantly, such associations do not establish that sustained mitokine signaling is itself maladaptive, and major mechanistic uncertainties remain, particularly for mitochondrial-derived peptides. We integrate these observations within a proposed \"mitokine code\" framework in which mitokine identity, relative patterns, temporal dynamics, and disease context may collectively provide information about mitochondrial stress and systemic adaptation. We further evaluate the potential and current limitations of mitokines as cardiovascular biomarkers and therapeutic targets. This framework positions mitokine signaling at the interface between mitochondrial dysfunction, systemic stress adaptation, and cardiovascular disease while identifying mechanistic and translational questions requiring prospective validation.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation-mediated silencing of MALAT1 promotes dexamethasone-induced growth plate chondrocyte ferroptosis via miR-124-3p/LPCAT3.","authors":"Xiaoju Liang, Lijun Zhang, Deliang Cheng","doi":"10.1007/s10863-026-10130-0","DOIUrl":"10.1007/s10863-026-10130-0","url":null,"abstract":"<p><p>Dexamethasone (Dex) causes growth plate injury and growth retardation in children, yet the underlying epigenetic and post-transcriptional mechanisms remain poorly defined. This study addresses this gap by dissecting the MALAT1/miR-124-3p/LPCAT3 axis in Dex-induced chondrocyte ferroptosis. Primary rat growth plate chondrocytes and 2-week-old male Sprague-Dawley rats were treated with Dex. DNA methylation of the MALAT1 promoter was assessed by MSP analysis. Gain- and loss-of-function studies, CCK-8, ferroptosis markers and luciferase reporter assays were performed in vitro. In vivo, tibial growth plate morphology, zone-specific heights, systemic growth parameters and LPCAT3 expression were evaluated. The results showed that Dex reduced chondrocyte viability and suppressed MALAT1 expression in a dose-dependent manner, accompanied by hypermethylation of one CpG islands in the MALAT1 promoter. Treatment with 5-Aza-2'-deoxycytidine (5-Aza) restored MALAT1 expression and reduced methylation levels. MALAT1 overexpression attenuated Dex-induced ferroptosis, as evidenced by decreased Fe²⁺ and MDA levels and restored SLC7A11 and Gpx4 expression. Mechanistically, MALAT1 directly binds to miR-124-3p, which targets LPCAT3. miR-124-3p mimics abolished the protective effects of MALAT1, while LPCAT3 overexpression reversed the inhibitory effects of miR-124-3p mimics on cell viability and ferroptosis markers. In vivo, Dex reduced growth plate thickness, tibial length, and body weight gain, while both MALAT1 overexpression and 5-Aza treatment attenuated these deficits and restored LPCAT3 expression. In conclusion, DNA methylation-mediated MALAT1 downregulation promotes Dex-induced chondrocyte ferroptosis via the miR-124-3p/LPCAT3 axis. Targeting this pathway may represent a preclinically promising therapeutic strategy that warrants further investigation in glucocorticoid-induced growth retardation in children.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BICC1 attenuates oxidative stress-induced osteogenic injury via regulation of the PDK/PDH axis in MC3T3-E1 cells.","authors":"Zhongshuang Liu, Aijie Chen, Baoxu Li, Shibin Li, Weibin Huang, Qi Xie, Fucheng Tao, Leyao Su, Kairan Zhu, Qi Liu, Lin Ma","doi":"10.1007/s10863-026-10135-9","DOIUrl":"10.1007/s10863-026-10135-9","url":null,"abstract":"<p><p>Oxidative stress-mediated impairment of osteoblast function is a critical pathological basis for the development and progression of various bone metabolic diseases. BicC family RNA binding protein 1 (BICC1) plays important roles in osteoblast function, however, the underlying mechanism remains unclear. This study aimed to investigate the protective role of BICC1 in oxidative stress-induced osteogenic injury and the underlying mechanism. An oxidative injury model was established in MC3T3-E1 cells using 300 µM hydrogen peroxide (H₂O₂). Bicc1 over-expressing lentivirus and the pyruvate dehydrogenase kinase isozyme (PDK) inhibitor dichloroacetate (DCA) were used for intervention. The osteoblast differentiation and mitochondrial membrane potential and apoptosis were measured by biochemical analysis and Alizarin Red S staining. RT-qPCR and Western blot were used to detect mRNA and protein levels of key molecules. RNA sequencing was performed to identify core targets and signaling pathways. H₂O₂ treatment significantly suppressed MC3T3-E1 cell viability and osteogenic differentiation, enhanced apoptosis, and up-regulated PDK1 expression as well as pyruvate dehydrogenase complex (PDH) phosphorylation. Bicc1 over-expression markedly alleviated H₂O₂-induced mitochondrial dysfunction and apoptosis, restored osteogenic differentiation, and inhibited the activation of the PDK1/PDH axis. Transcriptomic analysis showed that PDK1 was a key target molecule in Bicc1-regulated apoptosis and oxidative stress responses. Inhibition of PDK1 recapitulates the protective effect of BICC1 to oxidative stress injury in MC3T3-E1 cells. Bicc1 attenuates oxidative stress injury and promotes osteogenic differentiation in MC3T3-E1 cells, and may serve as a potential therapeutic target for osteoporosis.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of 3',4'-dihydroxyflavonol on blood-brain barrier ıntegrity and matrix remodeling in rats with transient bilateral carotid occlusion-ınduced ıschemia-reperfusion.","authors":"Delal Ezgi Akinci, Tugce Aladag, Saltuk Bugra Baltaci, Ebru Kübra Uzdil, Rasim Mogulkoc, Abdulkerim Kasim Baltaci","doi":"10.1007/s10863-026-10134-w","DOIUrl":"10.1007/s10863-026-10134-w","url":null,"abstract":"<p><p>The reduced blood flow and energy substrates to the affected area during ischemia and sudden exposure to these molecules after ischemia is called reperfusion. Reperfusion can be as damaging to cells and tissues as ischemia. This study aims to examine the effects of brain Ischemia-Reperfusion (I/R) and 1-week 3',4'-Dihydroxyflavonol (DiOHF) treatment on Matrix Metalloproteinasease (MMP), occludin, claudin-5, and β-actin levels in frontal cortex and hippocampus tissue in male rats. In this study, twenty-eight male Wistar-Albino rats were allocated into four experimental groups: Control, Sham, Ischemia-Reperfusion (I/R), and Ischemia-Reperfusion + DiOHF. Under general anesthesia, bilateral carotid artery ligation was performed to induce ischemia for 30 min, followed by reperfusion. DiOHF supplementation (10 mg/kg) was administered for one week. At the end of the treatment period, the animals were sacrificed under general anesthesia, and the frontal cortex and hippocampus tissues were harvested. Gene expression levels of MMP-3, MMP-9, occludin, claudin-5, and β-actin in the collected tissues were analyzed using real-time PCR. While I/R suppressed the levels of claudin-5 and occludin in the frontal cortex and hippocampus, it increased the levels of β-actin, matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9). 3',4'-Dihydroxyflavonol supplementation for 1 week corrected the deteriorations caused by I/R. The study results show that 1 week of 3',4'-Dihydroxyflavonol treatment after I/R corrects the changes in structural damage indicators caused by transient bilateral carotid occlusion-induced ischemia-reperfusion in the frontal cortex and hippocampus to a certain extent.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}